The existence of immune cells including macrophages and mast cells in rat ovary implies that various cytokines from these cells may play a role in ovarian functions. The aim of the present study was to investigate whether granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-1β are capable of stimulating histamine release and steroidogenesis in rat ovary, and to determine the sites of histamine production in the ovary. Histamine release from preovulatory ovarian tissues was stimulated in a dose-dependent manner at 3-30 ng/ml of GM-CSF in the presence of interleukin-1β (10 ng/ml). However, treatment with GM-CSF and interleukin-1β did not cause any significant change in the levels of ovarian steroids. Intense staining of histidine decarboxylase in the ovary was immunohistochemically detected in large granular cells on the morning of the pro-oestrus day. These results indicate that GM-CSF may be involved in the regulation of ovarian histamine secretion in mast cells partially by enhancing interleukin-1β-induced histamine release in the process of ovulation.